Long-term survival for a cohort of adults with cerebral palsy

The aim of this study was to investigate long-term survival and examine causes of death in adult patients with cerebral palsy (CP). A 1940–1950 birth cohort based on paediatric case referral allows for long-term survival follow-up. Survival is analyzed by birth characteristics and severity of disability from age 20 years (and age 2y for a subset of the data). Survival outcome compared with that expected in the general population based on English life tables. The main cohort consisted of 341 individuals, with 193 males and 148 females. Conditional on surviving to age 20 years, almost 85% of the cohort survived to age 50 years (a comparable estimate for the general population is 96%). Very few deaths were attributed to CP for those people dying over 20 years of age. Females survived better than males. However, females faced a greater increase in risk relative to the general population than did males. We conclude that survival outlook is good though lower than in the general population. The relative risk of death compared with the UK population decreases with age, although it shows some indication of rising again after age 50 years. Many more deaths were caused by diseases of the respiratory system among those dying in their 20s and 30s than would be expected in the general population. Many fewer deaths than expected in this age group are caused by injuries and accidents. For those people who die in their 40s and 50s, an increase in deaths due to diseases of the circulatory system and neoplasms is observed. More deaths than expected in this age group are due to diseases of the nervous system

Prediction of gene–phenotype associations in humans, mice, and plants using phenologs

All authors are with the Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX 78712, USA. -- Ulf Martin Singh-Blom is with the Program in Computational and Applied Mathematics, The University of Texas at Austin, Austin, TX 78712, USA, and th Unit of Computational Medicine, Department of Medicine, Karolinska Institutet, Stockholm 171 76, Sweden. -- Kriston L. McGary is with the Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USA.Background: Phenotypes and diseases may be related to seemingly dissimilar phenotypes in other species by means of the orthology of underlying genes. Such “orthologous phenotypes,” or “phenologs,” are examples of deep homology, and may be used to predict additional candidate disease genes. Results: In this work, we develop an unsupervised algorithm for ranking phenolog-based candidate disease genes through the integration of predictions from the k nearest neighbor phenologs, comparing classifiers and weighting functions by cross-validation. We also improve upon the original method by extending the theory to paralogous phenotypes. Our algorithm makes use of additional phenotype data — from chicken, zebrafish, and E. coli, as well as new datasets for C. elegans — establishing that several types of annotations may be treated as phenotypes. We demonstrate the use of our algorithm to predict novel candidate genes for human atrial fibrillation (such as HRH2, ATP4A, ATP4B, and HOPX) and epilepsy (e.g., PAX6 and NKX2-1). We suggest gene candidates for pharmacologically-induced seizures in mouse, solely based on orthologous phenotypes from E. coli. We also explore the prediction of plant gene–phenotype associations, as for the Arabidopsis response to vernalization phenotype. Conclusions: We are able to rank gene predictions for a significant portion of the diseases in the Online Mendelian Inheritance in Man database. Additionally, our method suggests candidate genes for mammalian seizures based only on bacterial phenotypes and gene orthology. We demonstrate that phenotype information may come from diverse sources, including drug sensitivities, gene ontology biological processes, and in situ hybridization annotations. Finally, we offer testable candidates for a variety of human diseases, plant traits, and other classes of phenotypes across a wide array of species.Center for Systems and Synthetic BiologyInstitute for Cellular and Molecular [email protected]

Cell cycle-dependent phosphorylation of Theileria annulata schizont surface proteins

The invasion of Theileria sporozoites into bovine leukocytes is rapidly followed by the destruction of the surrounding host cell membrane, allowing the parasite to establish its niche within the host cell cytoplasm. Theileria infection induces host cell transformation, characterised by increased host cell proliferation and invasiveness, and the activation of anti-apoptotic genes. This process is strictly dependent on the presence of a viable parasite. Several host cell kinases, including PI3-K, JNK, CK2 and Src-family kinases, are constitutively activated in Theileria-infected cells and contribute to the transformed phenotype. Although a number of host cell molecules, including IkB kinase and polo-like kinase 1 (Plk1), are recruited to the schizont surface, very little is known about the schizont molecules involved in host-parasite interactions. In this study we used immunofluorescence to detect phosphorylated threonine (p-Thr), serine (p-Ser) and threonine-proline (p-Thr-Pro) epitopes on the schizont during host cell cycle progression, revealing extensive schizont phosphorylation during host cell interphase. Furthermore, we established a quick protocol to isolate schizonts from infected macrophages following synchronisation in S-phase or mitosis, and used mass spectrometry to detect phosphorylated schizont proteins. In total, 65 phosphorylated Theileria proteins were detected, 15 of which are potentially secreted or expressed on the surface of the schizont and thus may be targets for host cell kinases. In particular, we describe the cell cycle-dependent phosphorylation of two T. annulata surface proteins, TaSP and p104, both of which are highly phosphorylated during host cell S-phase. TaSP and p104 are involved in mediating interactions between the parasite and the host cell cytoskeleton, which is crucial for the persistence of the parasite within the dividing host cell and the maintenance of the transformed state

Ariel - Volume 10 Number 5

Executive Editors Madalyn Schaefgen David Reich Business Manager David Reich News Editors Medical College Edward Zurad CAHS John Guardiani World Mark Zwanger Features Editors Meg Trexler Jim O\u27Brien Editorials Editor Jeffrey Banyas Photography and Sports Editor Stuart Singer Commons Editor Brenda Peterso

Measurements of vortex line density generated by a quartz tuning fork in superfluid 4^{4} 4 He

We present proof-of-concept measurements of the vortex line density generated by a quartz tuning fork resonator probed by the attenuation of second sound in superfluid 4He at 1.6 K. The force–velocity response of a quartz tuning fork operating at a frequency of 31 kHz exhibited the onset of extra damping at a velocity of 0.5 ms−1. Attenuation of the 5th resonant mode of second sound was observed at the same velocity, indicating the production of vortex lines. Our measurements demonstrate that an increase of the drag coefficient corresponds to the development of quantum turbulence

Dietary nitrate supplementation enhances short but not longer duration running time-trial performance

Purpose This study evaluated the effects of dietary nitrate (NO3-) supplementation on physiological functioning and exercise performance in trained runners/ triathletes conducting short and longer distance treadmill running time-trials (TT). Method Eight trained male runners or triathletes completed four exercise performance tests comprising a 10 minute warm up followed by either a 1500 m or 10,000 m treadmill TT. Exercise performance tests were preceded 3 hours before the exercise by supplementation with either 140 ml concentrated nitrate-rich (~ 12.5 mmol nitrate) (BRJ) or nitrate-deplete (~ 0.01 mmol nitrate) (PLA) beetroot juice. Results BRJ supplementation significantly elevated plasma [NO2-] (P 0.05). However, post-exercise blood [lactate] was significantly greater in BRJ following the 1500 m TT (6.6 ± 1.2 vs. 6.1 ± 1.5 mM; P 0.05). Performance in the 1500 m TT was significantly faster in BRJ versus PLA (319.6 ± 36.2 vs. 325.7 ± 38.8 s; P 0.05). Conclusion Acute BRJ supplementation significantly enhanced 1500 m but not 10,000 m TT performance. These findings suggest that BRJ might be ergogenic during shorter-distance TTs which allow for a high work rate, but not during longer-distance TTs, completed at a lower work rate

Nuclear hyaluronidase 2 drives alternative splicing of CD44 pre-mRNA to determine profibrotic or antifibrotic cell phenotype

The cell surface protein CD44 is involved in diverse physiological processes, and its aberrant function is linked to various pathologies such as cancer, immune dysregulation, and fibrosis. The diversity of CD44 biological activity is partly conferred by the generation of distinct CD44 isoforms through alternative splicing. We identified an unexpected function for the ubiquitous hyaluronan-degrading enzyme, hyaluronidase 2 (HYAL2), as a regulator of CD44 splicing. Standard CD44 is associated with fibrotic disease, and its production is promoted through serine-arginine–rich (SR) protein–mediated exon exclusion. HYAL2 nuclear translocation was stimulated by bone morphogenetic protein 7, which inhibits the myofibroblast phenotype. Nuclear HYAL2 displaced SR proteins from the spliceosome, thus enabling HYAL2, spliceosome components (U1 and U2 small nuclear ribonucleoproteins), and CD44 pre-mRNA to form a complex. This prevented double-exon splicing and facilitated the inclusion of CD44 exons 11 and 12, which promoted the accumulation of the antifibrotic CD44 isoform CD44v7/8 at the cell surface. These data demonstrate previously undescribed mechanisms regulating CD44 alternative splicing events that are relevant to the regulation of cellular phenotypes in progressive fibrosis

Cognitive Information Processing

Contains reports on five research projects.National Institutes of Health (Grant 5 PO1 GM-14940-02)National Institutes of Health (Grant 5 P01 GM-15006-02)Joint Services Electronics Programs (U. S. Army, U. S. Navy, and U. S. Air Force) under Contract DA 28-043-AMC-02536(E

On the metallicity dependence of crystalline silicates in oxygen-rich asymptotic giant branch stars and red supergiants

We investigate the occurrence of crystalline silicates in oxygen-rich evolved stars across a range of metallicities and mass-loss rates. It has been suggested that the crystalline silicate feature strength increases with increasing mass-loss rate, implying a correlation between lattice structure and wind density. To test this, we analyse Spitzer IRS and Infrared Space Observatory SWS spectra of 217 oxygen-rich asymptotic giant branch stars and 98 red supergiants in the Milky Way, the Large and Small Magellanic Clouds and Galactic globular clusters. These encompass a range of spectral morphologies from the spectrally-rich which exhibit a wealth of crystalline and amorphous silicate features to 'naked' (dust-free) stars. We combine spectroscopic and photometric observations with the GRAMS grid of radiative transfer models to derive (dust) mass-loss rates and temperature. We then measure the strength of the crystalline silicate bands at 23, 28 and 33 microns. We detect crystalline silicates in stars with dust mass-loss rates which span over 3 dex, down to rates of ~10^-9 solar masses/year. Detections of crystalline silicates are more prevalent in higher mass-loss rate objects, though the highest mass-loss rate objects do not show the 23-micron feature, possibly due to the low temperature of the forsterite grains or it may indicate that the 23-micron band is going into absorption due to high column density. Furthermore, we detect a change in the crystalline silicate mineralogy with metallicity, with enstatite seen increasingly at low metallicity.Comment: Accepted for publication in MNRAS, 24 pages, 16 figure